Skeletal System • Function: • Protection • Hematopoiesis • Mineral homeostasis • Calcium • Phosphorus • Carbonate • Magnesium
Structure • Bone is a connective tissue: • Matrix • Collagen fibers for flexibility and tensile strength • Calcium for rigidity • Hydroxyapatite Ca5(PO4)3OH
Cells: • Osteoblast • Form organic components of matrix • Osteocyte • Osteoblasts • From monocytes • Secrete citric and lactic acids • Collagenases and other enzymes • Stimulated by PTH • Inhibited by Calcitonin
Types of Bone • Dense or Compact (85%) • Osteon (Haversian System) • Central (Haversian) canal • Lamellae • Lacunae with osteocytes • Canaliculi • Spongy (cancellous) bone (15%) • trabeculae
Periosteum • Outer layer is dense, irregular CT with nerves and blood vessels • Inner layer • Osteoblasts • Anchored to bone by collagen fibers that penetrate into bone
Joints • Degree of movement • Synarthrosis – immovable joint • Amphiarthrosis – slightly movable joint • Diarthrosis – freely movable joint
Synovial joints • Joint capsule • Fibrous CT • Tendons and ligaments • Nerves, blood and lymph vessels • Synovial membrane • Loose fibrous CT • Many blood vessels – good repair • Joint (synovial) Cavity
Synovial fluid • Plasma filtrate • Synovial cells and leukocytes phagocytize debris and microbes • Articular cartilage • Reduce friction • Distribute force
Bone Pathophysiology • Inherited conditions: • Osteogenesis imperfecta • Inherited defect in collagen synthesis • Osteopenia and brittle bones • Often- defective tooth formation, blue sclera, faulty hearing, other defects • Inheritance can be dominant, recessive or by new mutation • Several degrees of severity ( I,II,III,IV) • Biphosphate treatment can improve bone mass in all types of the disorder
Achondroplasia • Involves a defect in normal cartilage development • Epiphyseal plates close early in long bones; individual has short arms and legs, but normal spine and skull • Dominant inheritance, but frequent new mutations • Other organs develop normally • Individuals live a normal lifespan
Acquired disorders • Osteoporosis – “porous bone” • Most common metabolic bone disease in North America • Can be attributed to genetics, diet or hormones • Most osteoporosis is idiopathic osteoporosis • Bone loss due to an identifiable cause is secondary osteoporosis • Bone tissue is mineralized normally, but over time the structural integrity of bone is lost and it becomes thinner and weaker, and more prone to fractures.
Key features: bone fracture and the associated pain. • WHO defines osteoporosis by bone density: • Normal bone > 833 mg/cm2 • Osteopenia 833 to 648 mg/cm2 • Osteoporosis < 648 mg/cm2 • Can be generalized, involving major portions of the axial skeleton • Can be regional, involving one segment of the appendicular skeleton
Remodeling is constant • Teen years more bone is laid down than reabsorbed • Peak bone mass or maximum density reached at around 30 years of age • After age 30, bone is reabsorbed faster than it is laid down (loss of about 0.7% /year) • In women, bone loss is most rapid in the first years after menopause, but continues throughout postmenopausal years • Est. 55% of people over 50 have osteoporosis or low bone mass.
Men also lose bone density, but start out with more bone mass so takes longer. • By age 90 about 17% of males have had a hip fracture, vs. 32 % of females • Vertebral fractures also occur → kyphosis • Most common in whites, but affects all races. • African Americans have about half the fracture rates of whites (higher peak bone mass)
Risk factors • Family history • White race • Increased age • Female sex • Small stature • Fair or pale skin • Thin build • Early menopause (natural or surgical) • Late menarche
Risk factors cont. • Nulliparity • Obesity • Weight below a healthy range • Acidosis • Low dietary calcium and vitamin D • High caffeine intake • Sedentary life style • Smoker • Excessive alcohol consumption • Liver, kidney disease, rheumatoid arthritis, etc.
Often progresses silently for decades until fracture occurs • Bones can fracture spontaneously • Most severe in spine, wrist and hips • Estrogens and androgens may be factors in both sexes • Testosterone is converted into estrogen in peripheral tissues and decreases bone loss • Rapid bone loss is osteoclast mediated • Slow bone loss is osteoblast mediated
Clinical manifestations • Pain and bone deformity • Kyphosis caused by vertebral collapse • Fractures of long bones • Fatal complications include fat or pulmonary embolism, pneumonia, hemorrhage and shock • 20 % die as a result of surgical complications
Treatment • No known cure • Slow bone loss and promote bone deposition • Calcium and vitamin D supplements • Nasal or subcutaneous calcitonin • Hormone replacement therapy • Biophosphates – inhibit osteoclasts • Dual x-ray absorptiometry for diagnosis • PREVENTION
Prevention • Intake of calcium, vitamin D, magnesium and possibly boron • Regular, weight-bearing exercise • Avoid tobacco and glucocorticoids • No alcoholism • Hormone replacement? • Parathyroid hormone? • Testosterone for men and possibly women
Rickets and Osteomalacia • Inadequate mineral deposition in essentially normal organic matrix • Softened bone: • Subject to malformation and distortion –pain
Rickets • Dietary vitamin D deficiency causes inadequate mineralization of the developing skeleton in infants and children • Rarely seen in Western nations • Poverty • Ignorance • Bones are soft and easily deformed • Tendency to fractures • Therapy: supply vitamin D and calcium
Osteomalacia • Rarely due to vitamin D deficiency • Usually GI malabsorption, renal defect or chronic kidney or liver diseases. • Elderly often affected due to inadequate diet or lack of outdoor activity • May accompany and complicate osteoporosis.
Joint Disorders • Osteoarthritis • Most common joint disease in North America • Minimal inflammatory component • Differentiated from inflammatory disease by: • Absence of synovial membrane inflammation • Lack of systemic signs and symptoms • Normal synovial fluid • Much of the pain and loss of mobility associated with aging.
Osteoarthritis • Incidence increases with age: 85% of people age 65 have some joint degeneration • Incidence similar, but women more severely affected • Exceptional stress on joints: gymnasts, etc. • Biochemical defect in cartilage • Malformed joint, obesity and postural defects • Genetic component • Torn ACL or meniscectomy
Osteoarthritis • When associated with known risk factors it is secondary OA • No risk factors – idiopathic OA • Pathological characteristics: • Erosion of the articular cartilage • Sclerosis of subchondral bone • Formation of bone spurs or osteophytes
Osteoarthritis • Begins in articular cartilage • Yellow-grey or brownish gray • Thin, irregular, frayed • Cracks or fissures develop (fibrillation) • Fluid filled cysts may form • Microfractures of subchondral bone • Formation of fibrocartilage repair plugs • Bone surface exposed • Bone responds by becoming dense and hard
Osteoarthritis • Synovial membrane is indirectly affected • Fragments of fibrocartilage cause inflammation –pain • Fibrous repair of joint capsule restricts motion • Osteophytes form – pain and loss of motion • Joint mice
Osteoarthritis • Affects one or more weight-bearing joints • Hand, wrist, lower cervical spine, lumbar spine and sacroiliac, hip, knees, ankles, feet • Aches and stiffness • Symptoms increase with activity; diminish with rest • Usually no swelling or redness of adjacent tissues • Sometimes nocturnal pain – may be referred
Osteoarthritis Primary signs and symptoms of joint disease are: pain, stiffness, enlargement or swelling, tenderness, limited range of motion, muscle wasting, partial dislocation, and deformity, crepitus
Osteoarthritis • Evaluation made through clinical assessment and radiologic studies, CT scan, arthroscopy and MRI • Treatment: • Glucosamine may decrease pain and slow or stop progression – 1500 mg/day • Chondroitin sulfate – questionable absorption
Osteoarthritis • Analgesics and antiinflammatory drugs (NSAIDs) • Injections of corticosteroids or sodium hyaluronate (to improve lubrication) • Range of motion exercises • Reduce aggravating factors • Weight loss • Use of cane, crutches or walker • Surgical removal of bone spurs, and other • Replacement of joint
Rheumatoid Arthritis • Systemic disease with prominent involvement of the joints • Inflammatory joint disease characterized by: • Inflammatory damage in the synovial membrane or articular cartilage • Systemic signs of inflammation: fever, leukocytosis, malaise, anorexia, hyperfibrinogenemia)
Rheumatoid Arthritis • Systemic autoimmune disease that causes chronic inflammation of connective tissue • Initially affects synovial membrane • Later articular cartilage, joint capsule, ligaments and tendons, and bone • Affects joints of hands, wrists, ankles, and feet, but shoulders, hips and cervical spine may also be involved • Systemic effects on heart, kidney, lungs, skin and other organs
Rheumatoid Arthritis • Mild to severe • Destroys and distorts joints • Reduces life expectancy • Remission and exacerbation • 1 – 2% of adult population • Women : men = 3:1 • Onset usually in 20’s or 30’s • Symptoms lessen during pregnancy • Seasonal variation
Rheumatoid Arthritis • Idiopathic disease • Immune-mediated destruction of joints • Rheumatoid factors (IgM and IgG) target blood cells and synovial membranes forming antigen-antibody complexes • Genetic predisposition • Possibly bacterial or viral infection (Epstein-Barr)
Rheumatoid Arthritis • Chronic inflammation of synovial membrane • Cellular proliferation and damage to the microcirculation • Synovial membrane becomes irregular • Swelling, stiffness and pain • Cartilage and bone destruction • Ankylosis or fusing of joint • Ligaments and tendons also affected